Impact of Translocator Protein 18 kDa (TSPO) Deficiency on Mitochondrial Function and the Inflammatory State of Human C20 Microglia Cells
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Published on: June 14, 2018
Stefanie Bader1, Thea Würfel1, Tatjana Jahner1
1Department of Psychiatry and Psychotherapy, University of Regensburg, 93053 Regensburg, Germany.
Abstract:
Microglia are the resident immune cells of the central nervous system. Upon stimulus presentation, microglia polarize from a resting to an activated state. Microglial translocator protein 18 kDa (TSPO) is considered a marker of inflammation. Here, we characterized the role of TSPO by investigating the impact of TSPO deficiency on human microglia. We used TSPO knockout (TSPO-/-) variants of the human C20 microglia cell line. We found a significant reduction in the TSPO-associated protein VDAC1 in TSPO-/- cells compared to control cells. Moreover, we assessed the impact of TSPO deficiency on calcium levels and the mitochondrial membrane potential. Cytosolic and mitochondrial calcium concentrations were increased in TSPO-/- cell lines, whereas the mitochondrial membrane potential tended to be lower. Assessment of the mitochondrial DNA copy number via RT-PCR revealed a decreased amount of mtDNA in the TSPO-/- cells when compared to controls. Moreover, the metabolic profiles of C20 cells were strongly dependent on the glycolytic pathway. However, TSPO depletion did not affect the cellular metabolic profile. Measurement of the mRNA expression levels of the pro-inflammatory mediators revealed an attenuated response to pro-inflammatory stimuli in TSPO-depleted cells, implying a role for the TSPO protein in the process of microglial polarization.
Insights
Translocator protein 18 kDa (TSPO) deficiency in human microglia alters mitochondrial function and reduces inflammatory responses. This suggests TSPO plays a key role in microglial activation and central nervous system inflammation.
Area of Science:
- Neuroscience
- Immunology
- Cell Biology
Background:
- Microglia are the primary immune cells in the central nervous system.
- Microglial activation, a process involving polarization from a resting to an activated state, is crucial for immune responses.
- Translocator protein 18 kDa (TSPO) is recognized as a marker for microglial inflammation.
Purpose of the Study:
- To investigate the functional role of TSPO in human microglia.
- To characterize the impact of TSPO deficiency on microglial cellular and mitochondrial functions.
- To determine TSPO's contribution to microglial inflammatory responses.
Main Methods:
- Utilized TSPO knockout (TSPO-/-) human C20 microglia cell line.
- Assessed VDAC1 protein levels, cytosolic and mitochondrial calcium concentrations, and mitochondrial membrane potential.
- Quantified mitochondrial DNA (mtDNA) copy number using RT-PCR.
- Analyzed cellular metabolic profiles and mRNA expression of pro-inflammatory mediators.
Main Results:
- TSPO deficiency led to reduced VDAC1 protein levels.
- Increased cytosolic and mitochondrial calcium concentrations were observed in TSPO-/- cells.
- A trend towards lower mitochondrial membrane potential and decreased mtDNA copy number was noted.
- TSPO depletion attenuated the pro-inflammatory response to stimuli without altering the metabolic profile.
Conclusions:
- TSPO plays a significant role in regulating mitochondrial function in human microglia.
- TSPO deficiency impacts microglial calcium homeostasis and mitochondrial integrity.
- TSPO is implicated in modulating the pro-inflammatory response of microglia, suggesting its involvement in neuroinflammation.
